APPLICANT'S DESCRIPTION There is strong experimental and epidemiologic evidence that estrogens unopposed by progesterone increase the risk of endometrial women. Because of their anti-estrogenic properties (through aromatase inhibition and increase of SHBG synthesis) and possible tumor growth inhibition properties, it has been proposed that ligands may protect against hormone-related cancers, in particular breast and endometrial cancers. The specific aim of this study is to assess whether serum levels of the main human ligand, enterolactone, are negatively associated with risk of endometrial cancer. The study will use the resource of an ongoing case-control study of endometrial cancer and endogenous androgens and estrogens, nested within 3 cohorts, the New York University Women's Health Study (NYUWHS) in New York, United States, the Northern Sweden Health and Disease Study (NSHDS) in Umea, Sweden, and the ORDET Study in Milan, Italy. This ongoing study is funded by NIH. Case subjects are all incident cases of endometrial cancer diagnosed within appropriate parent study dates. Two controls matching the case on parent cohort, menopausal status, age at enrollment (+/-6 months), and date of enrollment (+/-3 months) will be selected. Data on known risk factors are available. Serum samples (for the NYU WHS and the ORDET Study) or plasma samples (for the Umea Study) collected at the time of enrollment in the cohort, and stored at 300 C are available for biochemical assays. The assays will be performed in Finland by Dr. Adlercreutz, who developed, the assay methodology. It is expected that approximately 300 cases will be eligible for the study. The availability of this ongoing study offers a unique opportunity to address the specific aim rapidly and at a minimal cost.